The objective of this research program is to provide an understanding of the cellular and molecular mechanisms that underlie the ability of the visual areas of the adult cerebral cortex to be modified by neural activity. It is well known that the immature, developing visual cortex of the mammalian brain is capable of functional reorganization in response to the visual environment and ultimately neural activity. However, a number of recent studies suggest that the adult cerebral cortex (including the visual and somatosensory areas) can also undergo rapid adaptive functional reorganization in response to particular induced regimens of neural activity or in response to compromised activity. This functional reorganization can be detected at the level of the receptive field properties and synaptic efficacy of individual neurons in the adult visual cortex. There is potentially great benefit to be derived if the rules that govern these alterations in cellular function and their molecular substrates in the normal visual cortex can be discovered. Attempts to ultimately utilize these functions for restorative procedures in otherwise functionally compromised visual cortex, such as occurs in various forms of amblyopia, may benefit from rational protocols that make use of the adult brain's natural capacity for "plasticity". Toward this goal, we evaluate a model (the covariance hypothesis) that proposes that short periods of correlation of pre- and postsynaptic activity between adult visual cortical neurons can transiently strengthen their synaptic connections and uncorrelated activity can weaken their synaptic connections. In addition, we evaluate the ability of this effect to spread to neighboring neurons. Our related hypothesis is that such modulation of synaptic efficacy in the adult cortex is spatially restricted to synapses, depends on their activity profile and requires activation of a certain class of amino acid receptor (the N-methyl-D-aspartate receptor). This activation triggers the production of a gas in that region of the central nervous system, nitric oxide (NO), that diffuses to selectively regulate synaptic efficacy. We evaluate this in isolated slices of visual cortex and in an isolated synaptosomal preparation. We further investigate the mechanism of action of the NO molecule with respect to its ability to mediate release of various neurotransmitters (including catecholamine and excitatory amino acids) by synaptic terminals and to selectively target these terminals and impart a "memory" to them based on their activity profile at the time of the NO signal.